Innovative approaches were used to identify the specific pharmacological properties of heterodimeric metabotropic glutamate receptors composed of mGlu2 and mGlu4 subunits, and reveal their existence in a neuronal cell line and in perforant path terminals.
Whole endosome recording shows that chloride interacts with vesicular glutamate transporters as both allosteric activator and permeant ion, and although the mode of permeation differs, chloride and glutamate use a related conduction pathway.
Combination of glutaminase inhibitor CB-839 and ASCT2 inhibitor V-9302 showed efficient antitumor effect against glutamine addicted liver cancer cells via glutathione depletion and reactive oxygen species (ROS) induction.
During parallel fibre activity in vivo, postsynaptic mGluR1 receptors in molecular layer interneurons of the cerebellar cortex are engaged in a frequency-dependent manner and in concert with inotropic glutamate receptors.
Cryo-EM structures of unliganded SLC1A5 and its complex with glutamine in outward-facing state provide insights into the substrate specificity and transport mechanism and will be helpful for developing selective inhibitors.
Single molecule subunit counting, FRET and electrophysiology experiments reveal that metabotropic glutamate receptor subunits interact and rearrange at the level of the transmembrane domains in response to allosteric modulators.
Cell culture models widely used in cancer research do not reflect metabolism in tumors; by altering culture systems to better model tumor metabolism we find that environmental cystine promotes tumor glutamine metabolism.